Salvia miltiorrhiza causes tonic contraction in rat ileum through Ca2+-calmodulin pathway

Tsai, Ching-Chung; Huang, Shih-Che; Liu, Jong-Kang; Wang, Hsiu-Chuan; Tsai, Tsung-Yu; Tsai, Ping-Ju; Liu, Ching-Wen; Chang, Li-Ching

doi:10.1016/j.jep.2012.05.041

Cited by 7 publications

(6 citation statements)

References 26 publications

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“…Additionally, GRP was added to the muscle strips that were treated with either atropine or nifedipine. Furthermore, the neuronal Ca + channel blocker, CTX (1 μM), was used to pretreat the isolated sling muscle strips, and 15 min later, DTACPN-BN was added to the organ bath 27 28 29 .…”

Section: Methodsmentioning

confidence: 99%

Mechanism of bombesin-induced tonic contraction of the porcine lower esophageal sphincter

Tsai

Chang

Lin

et al. 2015

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Gastroesophageal reflux disease (GERD) is a disorder that is related to an incompetent lower esophageal sphincter (LES). Previous studies showed that bombesin could increase LES pressure in humans and opossums. The aim of the present study was to characterize the effects of bombesin on porcine LES contraction. We used the selective agonists, neuromedin B (NMB), gastrin-releasing peptide (GRP), and [D-Tyr6,Apa-4Cl11,Phe13,Nle14]bombesin-(6-14) (DTACPN-BN), as well as receptor antagonists of bombesin receptor subtype 2 (BB2), and 3 (BB3) for ex vivo contraction studies. Atropine, nifedipine, tetrodotoxin, and ω-conotoxin GVIA were used to explore the agonist-induced LES contraction mechanism. Reverse transcription polymerase chain reaction and immunohistochemistry were applied to detect bombesin receptor expression. Our results indicate that GRP and DTACPN-BN, but not NMB, induced tonic contractions of the porcine LES in a dose-dependent manner, and the contractions were inhibited with selective BB2 and BB3 antagonists. The GRP-induced contraction is mainly caused by L-type Ca2+ channel-mediated Ca2+ influx. However, DTACPN-BN-induced contractions are associated with neuronal conduction. RT-PCR and immunohistochemistry revealed that BB2 and BB3 were expressed in the porcine LES. Bombesin-induced tonic contraction of the LES is mediated through BB2 and BB3. Bombesin, BB2, and BB3 agonists might have the potential to treat GERD.

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Section: Methodsmentioning

confidence: 99%

Mechanism of bombesin-induced tonic contraction of the porcine lower esophageal sphincter

Tsai

Chang

Lin

et al. 2015

Sci Rep

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“…Measurements of contraction of the isolated LES were performed according to the procedure previously described in detail [16,27]. Sprague-Dawley (SD) rats, each weighing 350–400 g, were euthanized with CO 2 directly in a sealed plastic bag and confirmed to be dead through observation of discontinuation of respiration and palpation of cessation of heartbeat.…”

Section: Methodsmentioning

confidence: 99%

“…Ca 2+ -free Krebs-Henseleit solution had a similar composition of Krebs-Henseleit solution except for the Ca 2+ and it contained 0.5 mM EGTA. The solution in organ bath was replaced by Ca 2+ -free Krebs-Henseleit solution with EGTA and SM extracts were added into organ baths [16,30].…”

Section: Methodsmentioning

confidence: 99%

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Salvia miltiorrhiza Induces Tonic Contraction of the Lower Esophageal Sphincter in Rats via Activation of Extracellular Ca2+ Influx

et al. 2015

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Up to 40% of patients with gastroesophageal reflux disease (GERD) suffer from proton pump inhibitor refractory GERD but clinically the medications to strengthen the OPEN ACCESSMolecules 2015, 20 14505 lower esophageal sphincter (LES) to avoid irritating reflux are few in number. This study aimed to examine whether Salvia miltiorrhiza (SM) extracts induce tonic contraction of rat LES ex vivo and elucidate the underlying mechanisms. To investigate the mechanism underlying the SM extract-induced contractile effects, rats were pretreated with atropine (a muscarinic receptor antagonist), tetrodotoxin (a sodium channel blocker), nifedipine (a calcium channel blocker), and Ca 2+-free Krebs-Henseleit solution with ethylene glycol tetraacetic acid (EGTA), followed by administration of cumulative dosages of SM extracts. SM extracts induced dose-related tonic contraction of the LES, which was unaffected by tetrodotoxin, atropine, or nifedipine. However, the SM extract-induced LES contraction was significantly inhibited by Ca

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“…SM suppresses the colon inflammation induced by dextran sulfate sodium in rats (7) and alleviates the pathological changes in the intestine, thymus, and spleen and promotes recovery in rats with acute pancreatitis (8). SM causes intestinal contraction owing to an intracellular ca 2+ concentration-and ca 2+ -calmodulin-dependent mechanism (9) and the contraction of the lower esophageal sphincter via an extracellular ca 2+ influx-dependent mechanism (10).…”

Section: Introductionmentioning

confidence: 99%

Salvia miltiorrhiza induces depolarization of pacemaker potentials in murine small intestinal interstitial cells of Cajal via extracellular Ca²⁺ and Na⁺ influx

et al. 2021

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interstitial cells of cajal (iccs) are pacemaker cells that control smooth muscle contraction in the gastrointestinal (Gi) tract. The present study investigated the effects of Salvia miltiorrhiza (SM) on the pacemaker potentials of iccs from the mouse small intestine in vitro and on Gi motility in vivo. The whole-cell patch-clamp configuration was used to record pacemaker potential in iccs in vitro, and Gi motility was investigated in vivo by recording intestinal transit rate (ITR). Using the whole-cell patch-clamp configuration, SM depolarized the pacemaker potentials of iccs in a dose-dependent manner. Fulvestrant blocked SM-induced effects but 1,3-dihydro-3,3-bis(4-hydroxyphenyl)-7methyl-2H-indol-2-one did not. additionally, 4-[2-phenyl-5,7-bis(trifluoromethyl) pyrazolo[1,5-a]pyrimidin-3-yl] phenol blocked SM-induced effects. intracellular guanosine 5'-o-(2-thiodiphosphate), and pretreatment with extracellular ca 2+ -and na + -free solutions also blocked SM-induced effects. Furthermore, iTr values were increased by SM in vivo and SM elevated the levels of motilin (MTl). The SM-induced increase in iTr was associated with increased protein expression levels of c-kit and the transmembrane protein 16a (TMeM16a) channel. in addition, SM induced pacemaker potential depolarization through estrogen receptor β in a G protein-dependent manner via extracellular ca 2+ and na + regulation in the murine small intestine in vitro. Moreover, SM increased the iTr in vivo through the MTl hormone via c-kit and TMeM16a-dependent pathways. Taken together, these results suggested that SM may have the ability to control Gi motility and could be used as a Gi motility regulator.

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Salvia miltiorrhiza causes tonic contraction in rat ileum through Ca2+-calmodulin pathway

Cited by 7 publications

References 26 publications

Mechanism of bombesin-induced tonic contraction of the porcine lower esophageal sphincter

Mechanism of bombesin-induced tonic contraction of the porcine lower esophageal sphincter

Salvia miltiorrhiza Induces Tonic Contraction of the Lower Esophageal Sphincter in Rats via Activation of Extracellular Ca2+ Influx

Salvia miltiorrhiza induces depolarization of pacemaker potentials in murine small intestinal interstitial cells of Cajal via extracellular Ca²⁺ and Na⁺ influx

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Salvia miltiorrhiza causes tonic contraction in rat ileum through Ca2+-calmodulin pathway

Cited by 7 publications

References 26 publications

Mechanism of bombesin-induced tonic contraction of the porcine lower esophageal sphincter

Mechanism of bombesin-induced tonic contraction of the porcine lower esophageal sphincter

Salvia miltiorrhiza Induces Tonic Contraction of the Lower Esophageal Sphincter in Rats via Activation of Extracellular Ca2+ Influx

Salvia miltiorrhiza induces depolarization of pacemaker potentials in murine small intestinal interstitial cells of Cajal via extracellular Ca2+ and Na+ influx

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Salvia miltiorrhiza induces depolarization of pacemaker potentials in murine small intestinal interstitial cells of Cajal via extracellular Ca²⁺ and Na⁺ influx